255. Breakthrough Mucormycosis (BT-MCR) on Antifungals Having Mucorales Activity Portrays Worse Prognosis compared with BT-MCR on Mold-Active Antifungals with no Mucorales Activity

Abstract Background BT-MCR is known to develop in the setting of agents having Aspergillus but no Mucorales activity. However, BT-MCR can occur even with the use of antifungals having with Mucorales activity in patients with hematologic malignancies and or stem cell transplant (HM). Methods We reviewed the records of HM patients treated for MCR (1994 to 2019) at MD Anderson Cancer Center. We identified patients with BT-MCR on antifungals having Mucorales activity: posaconazole (POSA), isavuconazole (ISA), and amphotericin B (AMB) (group A), and patients with BT-MCR on agents having Aspergillus but no Mucorales activity: voriconazole (VRC), itraconazole (ITZ), echinocandins (group B). BT-MCR was defined as MCR diagnosis (dx) after ≥7days (d) of antifungal use. The primary outcome was 42d mortality after the BT-MCR dx. Chi-square or Fisher’s exact test was used for categorical variables and Wilcoxon rank-sum test used for continuous variables. Cox regression model was used to evaluate the independent variables on outcome. Results We identified 11 patients in group A (3 POSA, 5 ISA, 3 AMB) and 81 patients in group B (61 VRC, 13 echinocandins, 7 ITZ). Both groups were not different in terms of age, sex, underlying HM (AML/MDS in 100% vs. 88% in groups A and B, respectively), status of HM (active disease in 82% vs. 67%), prior stem cell transplant (45% vs. 54%) or GvHD (80% vs. 84%), neutropenia at dx (55% vs. 42%), prior receipt of >600 mg of prednisone (45% vs. 41%) or ICU at MCR dx (36% vs. 26%). Similarly, Mucorales species (Rhizopus spp. in 55% vs. 49%) and type of infection (sino-pulmonary in 73% vs. 68%) were no different between the groups. However, both d42 (82% vs. 46%, P = 0.025) and d84 (100% vs. 60%, P = 0.007) mortality was worse in group A. Similarly, median time to death was faster in patients in group A (26d, range 7-80d), vs. group B (42d, range 4–3146d, P = 0.031). Kaplan–Meier analysis showed a similar difference (Figure 1). In multivariate analysis, neutropenia (P = 0.038) and ICU at dx (P = 0.002) were independent factors on day 42d mortality in all 92 patients with prior Mucorales–active antifungals showing a trend associated with poor outcome (P = 0.17). Conclusion BT-MCR on agents having Mucorales activity is a marker of poor prognosis in HM patients. Early use of investigational immunotherapy and salvage antifungal chemotherapy studies is needed in that subgroup of patients. Disclosures All authors: No reported disclosures.

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Impact of metformin use in the outcomes of multiple myeloma patients post stem cell transplant.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.8034 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 8034-8034

Author(s):

Narjust Duma ◽

Jesus Vera Aguilera ◽

Jonas Paludo ◽

Yucai Wang ◽

Theodora Anagnostou ◽

...

Keyword(s):

Multiple Myeloma ◽

Multivariate Analysis ◽

Stem Cell ◽

Stem Cell Transplant ◽

Plasma Cells ◽

Cox Regression ◽

Hematologic Malignancies ◽

Cell Transplant ◽

Kaplan Meier ◽

The Us

8034 Background: Multiple myeloma (MM), a monoclonal plasma cell disorder, is one of the most common hematologic malignancies in the US. In preclinical studies, metformin demonstrated plasma cells cytotoxicity. However, there is lack of studies translating the effect of metformin into the clinical setting. Therefore, we assessed the clinical effect of metformin in patients (pts) with MM. Methods: All MM pts who underwent stem cell transplant (SCT) at the Mayo Clinic Rochester from 2007 to 2012 were reviewed. Patients were grouped based on metformin use. Initial diagnosis at our institution and ≥12 months of follow up were required. Kaplan-Meier method and Cox regression were used for time-to-event and multivariate analysis. Results: Out of 687 pts, 78 (11.4%) were using metformin at the time of MM diagnosis. Baseline characteristics in the metformin (Mt) and no-metformin (NMt) groups were similar (Table). Median (M) metformin dose was 2000 mg daily and m duration of metformin use from MM diagnosis was 22 months. Pts on the Mt group achieved higher rates of CR after SCT (41% vs. 29%, p<0.02). Median PFS after SCT was longer in the Mt group, 31.3 months (95% CI: 10.4-52.2) vs. 16.6 months in the NMt group (95%CI: 14.5-18.7) p<0.04. There was a trend towards longer OS in the Mt group, but it was not statistically significant (170 vs. 106 months, p<0.10). In a multivariate analysis of metformin use, age, ISS, LDH, and cytogenetics/FISH, the former was an independent predictor of PFS after SCT (OR: 0.38, 95%CI: 0.20-0.68, p<0.001). Conclusions: Metformin use was associated with a better PFS and higher CR after SCT in our MM cohort. A trend towards better OS was also noted in the Mt group. Larger studies are needed to enhance our understanding of the clinic effect of metformin on MM. [Table: see text]

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Characteristics of Multiple Myeloma Patients with Multiple Lines of Therapy Using Real-World US Claims Data

Blood ◽

10.1182/blood.v126.23.4519.4519 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4519-4519

Author(s):

Eric Maiese ◽

Brian Macomson ◽

Chris Kozma ◽

Terra Slaton ◽

Mekre Senbetta

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplant ◽

Treated Group ◽

Initial Therapy ◽

Categorical Variables ◽

Administrative Claims ◽

Cell Transplant ◽

Continuous Variables ◽

Hiv Diagnosis

Abstract Background: Multiple myeloma is an incurable disease with poor survival rate. Recently, novel treatments have focused on addressing unmet needs among heavily pre-treated patients who have failed prior therapies. The purpose of this analysis was to describe the characteristics of patients who are heavily pre-treated vs patients who were not, within 2 years of initiating MM therapy. Results of this analysis will help to understand the characteristics, including treatment patterns and burden, of MM patients who progress through lines of therapy over a relatively short time period. Methods: Using a US administrative claims database (Truven Health MarketScan® Database), adult patients (age ≥18) were included in the analysis if they had 1) ≥2 MM diagnoses codes (ICD-9 203.0x) on different dates between Jan 1, 2005-Mar 31, 2014 (study period); 2) MM treatment between Jan 1, 2007-Mar 31, 2012 and within 90 days of an MM diagnosis code (date of the first MM treatment set as the index date); and 3) continuous eligibility for medical insurance 24 months pre/postindex. Patients were excluded if they had 1) MM treatment during 24 months preindex; or during 24 month pre/post index had 2) moved from commercial insurance to Medicare; 3) non-MM chemotherapy; 4) pregnancy-related or stem cell transplant codes; or 5) HIV diagnosis during study period. An algorithm using dispensing dates and days supply was developed to define line of therapy (LOT) and double refractory. A new LOT was identified where there was a ≥60 day gap with no treatment, a ≥60 day gap followed by retreatment with the same drug, or where there was a change in therapy based on 30 day windows and the summed days supply of medication was >60 days. Refractory events were defined when a PI or IMiD had days supply for <60 days, was discontinued for ≥60 days, a different PI or IMiD was initiated and the initial drug did not appear in the next LOT. Heavily pre-treated was defined as starting an LOT after having received ≥3 prior LOT that included a PI and IMiD or double refractory to both PI and IMiD. Chi-square test was used to test for differences in categorical variables and Mann Whitney U test for continuous variables. Results: A total of 1109 patients were included in the analysis. The percent of patients with 1, 2, 3, 4 or >4 LOT were 39.8%, 33.0%, 15.4% and 6.1% and 5.7%, respectively. A single refractory event occurred in 66 (6.0%) patients and 2 (0.2%) patients were identified as double refractory. There were 80 (7.2%) patients who were heavily pre-treated. The heavily pre-treated group had a similar percent of males (56.3%) as the non-heavily pre-treated group (54.9%; p=0.82). The heavily pre-treated group was slightly younger (66.1 vs 70.9 years; p=0.0008) and had a lower percent with Medicare coverage (55.0% vs 71.1%; p=0.0024). The heavily pre-treated group had a substantially higher percent of regimens that included both PI and IMiD in the 1st LOT (28.8% vs 7.4%; p<0.0001). The most common 1st LOT drug regimens for the heavily pre-treated group were bortezomib (BOR) (21.31%), thalidomide (THAL) (21.3%), lenalidomide/bortezomib (LEN/BOR) (20.0%), and lenalidomide (LEN) (18.8%). In the non-heavily pre-treated group the most common 1st LOT regimens were LEN (36.7%), BOR (20.4%), THAL (14.4%), and melphalan (10.1%). Patients who were heavily pre-treated reached their 2nd LOT in fewer days than non-heavily pre-treated (152.5 vs 279.9 days; p<0.0001). There was a much higher percent of patients using BOR/LEN in the 2nd LOT in the heavily pre-treated than non-heavily pre-treated (20.0% vs. 4.1%). Conclusions: In this analysis, 7.2% of non-stem cell transplant patients were heavily pre-treated at 2 years after initiating MM therapy. Heavily pre-treated patients had a faster time to initiation of 2nd LOT. They also tended to be younger. Moreover, heavily pre-treated patients were more likely to have had both a PI and IMiD as their initial therapy. Patients who were heavily pre-treated in this analysis may have had faster disease progression, which may have led to becoming heavily pre-treated within the follow-up time of the study. Additional research should further explore the disease and economic burden of these patients. Disclosures Maiese: Janssen Scientific Affairs, LLC: Employment. Macomson:Janssen Scientific Affairs, LLC: Employment. Kozma:Janssen Scientific Affairs, LLC: Consultancy. Slaton:Janssen Scientific Affairs, LLC: Consultancy. Senbetta:Janssen Scientific Affairs, LLC: Employment.

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Immune Therapies for Hematologic Malignancies

Cancers ◽

10.3390/cancers13020295 ◽

2021 ◽

Vol 13 (2) ◽

pp. 295

Author(s):

Matthew J. Olnes

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Hematologic Malignancies ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Immune Therapies

The era of immunotherapy for hematologic malignancies began with the first allogeneic hematopoietic stem cell transplant (HSCT) study published by E [...]

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